Sex determination

Jonathan Wolfe

http://www.ucl.ac.uk/~ucbhjow

Objectives

At the end of this lecture you should:• know in outline the developmental steps in human sex

determination • be able to describe the evolution of the mammalian Y

chromosome and the SRY gene. • be able to describe the roles of the genes SRY, DAX1, and

SOX9.• Be able to describe the genes involved in sex

determination in Drosophila• Be able to describe the gene DMRT1 and its relatives

Reading• http://www.hgmp.mrc.ac.uk/omim/searchomim.html Search here for any of the genes

mentioned. • Goodfellow, P. N.; Lovell-Badge, R. 1993: SRY and sex determination in mammals.

Ann. Rev. Genet. 27 71-92 • Koopman, P.; Gubbay, J.; Vivian, N.; Goodfellow, P.; Lovell-Badge, R. 1991: Male

development of chromosomally female mice transgenic for Sry. Nature 351 117-121. • Wunderle, V. M.; et al. 1998: Deletion of long-range regulatory elements upstream of

SOX9 causes campomelic dysplasia. Proc. Nat. Acad. Sci. 95: 10649-10654. • Jennifer A. Marshall Graves 2002: The rise and fall of SRY Trends in Genetics 18: 259-

264 • David Zarkower 2001 Establishing sexual dimorphism: conservation amidst diversity?

Nature Reviews Genetics 2 175-185• Peter Koopman and Kelly A. Loffler, 2003, Sex Determination: The Fishy Tale of

Dmrt1 Current Biology, 13: R177 - R179• Haag ES, Doty AV (2005) Sex Determination across Evolution: Connecting the Dots.

PLoS Biol 3(1): e21

Comparison between Drosophila and Humans

karyotype Drosophila Human

2A XX female female

2A XY male male

2A XO male female

2A XXX female female

2A XXY female male

Gonadal differentiation

Y chromosomal genes

Genomic structure of SRY genes

Evolution of the Y chromosome and SRY

The loss of Y chromosomal genes

Sex determination in Drosophila

Another human gene

DMRT1 expression

Chicken Z = Human chr.9

DMRT1 expression in alligator